We propose to study the effect on the immune system of transplantable plasmacytomas in mice, an animal model of malignancy with many analogies to multiple myeloma in humans. Mice with plasmacytomas (PC) and humans with multiple myeloma have a severely depressed ability to mount an immune response. Our studies have led us to postulate that this PC-induced immunosuppression is mediated by a soluble factor. Our work is designed to determine whether the malignant plasma cells themselves produce this factor or whether the tumor cells effect this depression indirectly by activating other, non- malignant cells which then synthesize this regulatory product. In addition, we propose to develop an in vitro assay for this factor and to characterize it physically and functionally. Bibliographic references: Susan Zolla and David Naor: Restoration of immune competence in tolerant mice by parabiosis to normal mice. J. Exptl. Med.-, 140, 1421, 1974. Susan Zolla, F. Falkenberg, D. Naor: Is Tolerance an Active or Defective State? Transplantation Proceedings, 7, Suppl. 1, 381, 1975.